The goal of this project is to identify olfactory receptors that enable the Dengue Fever Mosquito to be attracted to humans. The proposed research promises to (1) provide insight into the genetic basis of mosquito attraction to humans and (2) provide specific information useful for preventing the spread of human disease by mosquitoes. The research plan builds on my recently published discovery that orco mutant mosquitoes retain strong attraction to humans despite lacking a functional odorant receptor pathway. The hypothesis I propose is that the ionotropic receptor (IR) pathway that is retained in orco mutants is essential for mosquito attraction to humans. Using olfactometer assays, I will identify which of the three IR co-receptors are required for mosquito attraction to human odor. I will then map the expression of IRs in mosquito olfactory organs using tissue-specific RNA-seq and whole mount in situ hybridization. By combining loss-of-function behavioral studies with an IR expression map, I will identify IRs that are candidate human odor receptors. Candidate human odor-selective IRs and their cognate IRCOs will be functionally reconstituted in heterologous cells and deorphanized using human odor components. Identifying behaviorally relevant mosquito receptors and the human odors that activate them will provide molecular insights that can be used to make mosquito behavior less harmful.